The Role of Pancreatic Development in Modeling Pancreatic Disease in Mice. September 4-5, 2003 Northwestern University and Northwestern Memorial Hospital The pancreas serves both an endocrine and exocrine function and has distinct roles in glucose homeostasis and digestion. Several debilitating diseases, with virtually no curative measures, arise when cell types undergo genetic mutations, altering cell function and/or inducing cellular transformation. Diabetes, pancreatitis, and pancreatic cancer have serious health consequences beginning with a greatly reduced quality of life and ending in death. These diseases are associated with each other. For example, people with diabetes and/or pancreatitis have a greater incidence of pancreatic cancer. In order to introduce curative paradigms against these diseases, it is critical to evaluate therapies outside the clinic, which include using animal models that recapitulate these human diseases. A few mouse models do exist for these diseases yet seldom do these models provide phenotypic or molecular mimicry to their human counterpart. To better understand the sequential genetic and cellular events that lead to diabetes, pancreatitis, and pancreatic cancer and engineer models for therapeutic evaluation, it becomes critical to understand the underlying mechanisms responsible for differentiation and cell fate. Evidence is accumulating on the pathway from a progenitor cell type to the three primary cells of the pancreas: islet, acinar, and ductal cells. In order to improve pancreatic development and disease modeling research, I propose holding a conference that brings both groups together. I am hoping to foster a critical link that is not entirely in place. That link is between scientists exploring pancreatic development and the signals that determine differentiation patterns and cell fate with those investigators who desire to model pancreatic disease in mice. New information that defines which embryonic cell(s) and/or cell signal(s) that are responsible for generating mature endocrine and exocrine cells in the pancreas is critical for engineering new transgenic mouse models that recapitulate diabetes, pancreatitis, and pancreatic cancer. Targeting pancreatic progenitor cells with various genetic alterations will provide valuable information for the developmental biologist and clinical pathologist alike.